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First-in-human stud...
First-in-human study with intratumoral administration of a CD40 agonistic antibody, ADC-1013, in advanced solid malignancies
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- Irenaeus, Sandra (författare)
- Uppsala universitet,Experimentell och klinisk onkologi
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- Nielsen, Dorte (författare)
- Herlev Gentofte Hosp, Dept Oncol, Herlev, Denmark
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- Ellmark, Peter (författare)
- Medicon Village, Alligator Biosci AB, Lund, Sweden
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- Yachnin, Jeffrey (författare)
- Karolinska Institutet
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- Deronic, Adnan (författare)
- Medicon Village, Alligator Biosci AB, Lund, Sweden
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- Nilsson, Anneli (författare)
- Medicon Village, Alligator Biosci AB, Lund, Sweden
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- Norlen, Per (författare)
- Medicon Village, Alligator Biosci AB, Lund, Sweden
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- Veitonmaki, Niina (författare)
- Medicon Village, Alligator Biosci AB, Lund, Sweden
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- Wennersten, Camilla S. (författare)
- Medicon Village, Alligator Biosci AB, Lund, Sweden
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- Ullenhag, Gustav (författare)
- Uppsala universitet,Experimentell och klinisk onkologi
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(creator_code:org_t)
- 2019-03-08
- 2019
- Engelska.
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Ingår i: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 145:5, s. 1189-1199
- Relaterad länk:
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https://onlinelibrar...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Agonistic CD40 antibodies activate dendritic cells and can expand and activate tumor-specific T cells. Our purpose was to assess the CD40 agonistic antibody ADC-1013 in the clinical setting including intratumoral administration since preclinical studies have indicated that intratumoral is better than intravenous administration. A Phase I, open label, multicenter study was conducted in patients with advanced solid tumors who had received established treatments. A modified 3 + 3 dose-escalation was applied (every other week dosing). Twenty-three patients were treated with ADC-1013 intratumorally (dosing from 22.5 mu g/kg up to 400 mu g/kg) or intravenously (dosing at 75 mu g/kg). The pharmacodynamic effects observed in the patients were further verified in an hCD40tg mouse model. Adverse events were mostly Common Terminology Criteria for Adverse Events (CTCAE) Grades 1 or 2 and transient. The serum concentration ADC-1013 and cytokine release (MCP-1, TNF alpha and IL-6) were more pronounced in patients receiving injections in deep metastases compared to patients receiving injections in superficial metastases. Treatment with ADC-1013 resulted in a marked decrease in B cell levels in peripheral blood after 24 h while remaining B cells significantly increased their expression of the cell surface activation marker CD86. Activation of antigen-presenting cells and subsequent activation of T cells were demonstrated in hCD40tg mice. Moreover, ADC-1013 treatment in this mouse model acted synergistically with a PD-1 inhibitor. The results from the first-in-human study of ADC-1013 indicate that intratumoral administration of ADC-1013 into superficial lesions is well tolerated at clinically relevant doses and associated with pharmacodynamic responses.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- agonistic antibody
- CD40
- phase I study
- metastatic cancer
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Irenaeus, Sandra
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Nielsen, Dorte
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Ellmark, Peter
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Yachnin, Jeffrey
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Deronic, Adnan
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Nilsson, Anneli
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visa fler...
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Norlen, Per
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Veitonmaki, Niin ...
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Wennersten, Cami ...
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Ullenhag, Gustav
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Cancer och onkol ...
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- Av lärosätet
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Uppsala universitet
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Karolinska Institutet